Preparation of crosslinked polymers containing biomass derived materials

ABSTRACT

Processes for preparing crosslinked polymers using biomass derived materials, such as aldaric acids and derivatives, are provided. The polymers can be used as hydrogels.

FIELD OF INVENTION

The invention is directed to the preparation of novel, crosslinkedpolymers using biomass derived materials, such as aldaric acids andderivatives. These polymers can be used as hydrogels.

BACKGROUND

The concept of using biomass-derived materials to produce other usefulproducts has been explored since man first used plant materials andanimal fur to make clothing and tools. Biomass derived materials havealso been used for centuries as adhesives, solvents, lighting materials,fuels, inks/paints/coatings, colorants, perfumes and medicines.Recently, people have begun to explore the possibility of using “refinedbiomass” as starting materials for chemical conversions leading to novelhigh value-in-use products. Over the past two decades, the cost ofrenewable biomass materials has decreased to a point where many arecompetitive with those derived from petroleum. In addition, manymaterials that cannot be produced simply from petroleum feedstocks arepotentially available from biomass or refined biomass. Many of theseunique, highly functionalized, molecules would be expected to yieldproducts unlike any produced by current chemical processes. “Refinedbiomass” is purified chemical compounds derived from the first or secondround of plant biomass processing. Examples of such materials includecellulose, sucrose, glucose, fructose, sorbitol, erythritol, and variousvegetable oils.

A particularly useful class of refined biomass is that of aldaric acids.Aldaric acids, also known as saccharic acids, are diacids derived fromnaturally occurring sugars. When aldoses are exposed to strong oxidizingagents, such as nitric acid, both the aldehydic carbon atom and thecarbon bearing the primary hydroxyl group are oxidized to carboxylgroups. An attractive feature of these aldaric acids includes the use ofvery inexpensive sugar based feedstocks, which provide low raw materialcosts and ultimately could provide low polymer costs if the properoxidation processes are found. Also, the high functional density ofthese aldaric acids provide unique, high value opportunities, which arecompletely unattainable at a reasonable cost from petroleum based feedstocks.

Hydrogels (hydrated gel) are polymers that contain water-swellable,three-dimensional networks of macromolecules held together by covalentor noncovalent (e.g., ionic or hydrogen bonded) crosslinks. Uponplacement in an aqueous environment, these networks swell to the extentallowed by the degree of crosslinking. They are used in many fields suchas medical applications, personal care formulations, coatings, andsurfactants.

U.S. Pat. No. 5,496,545 discloses crosslinked polyallylamine andpolyethyleneimine. The crosslinking agents disclosed includeepichlorohydrin, diepoxides, diisocyanates, α,ω-dihaloalkanes,diacrylates, bisacrylamides, succinyl chloride, and dimethyl succinate.Applicants have invented a process to prepare new crosslinked polymersthat can function as hydrogels, using crosslinking moieties that couldbe derived from biomass sources.

SUMMARY OF THE INVENTION

One aspect of the invention is a process for preparing a crosslinkedpolymer, comprising contacting a crosslinking agent with a substratepolymer to form a crosslinked polymer; wherein the crosslinking agent isselected from compounds having Formulae VI, VII and VIII:

wherein L and L′ independently contain a suitable functional group, andn=1-6, m=0-4, and p=1-4;

-   -   and the substrate polymer comprises:    -   a linear, branched or cyclic polymeric backbone comprising        repeat units that comprise one or more of hydrocarbylene groups,        heteroatoms, and carbonyl carbon groups;    -   wherein the hydrocarbylene groups are aliphatic or aromatic,        linear, branched, or cyclic, or combinations thereof; and    -   reactive pendant groups attached to the polymeric backbone, the        pendant groups being of the formula -G or —R-G,    -   wherein G is a nucleophile or electrophile;    -   wherein R is independently linear, cyclic, or branched alkylene,        arylene, or alkarylene groups of 1-22 carbon atoms, optionally        substituted with alkyl, aryl, hydroxy, amino, carbonyl, ester,        amide, alkoxy, nitrile or halogen, and optionally containing        —O—, ‘3Si(ZZ′)O—, —(C═O)— or —NZ- linkages, where Z and Z′ are        independently hydrogen, alkyl, substituted alkyl, alkaryl,        substituted alkaryl, aryl, or substituted aryl. The        hydrocarbylene groups and heteroatoms of the repeat units are        optionally substituted with substituents that comprise one or        more of C₁-C₃₀ hydrocarbylene groups, heteroatoms, and carbonyl        carbon groups. The hydrocarbylene groups of the substituents are        aliphatic or aromatic, linear, branched, or cyclic, or mixtures        thereof.

Preferably the suitable functional groups contained by L and L′ arederived from an amine, hydroxyl, carboxylic acid, ester, urethane, urea,amide, or isocyanate; and G is an epoxide, isocyanate, benzylic halide,amine, acid halide, ester, or amide. Also preferably L and L′ areselected from the group consisting of optionally substituted —NHR″,—OR″, and hydrocarbylene-C(═O)OR″; and G is selected from the groupconsisting of —NH₂, —C(═O)Cl, —C(═O)OR″, or —C(═O)NH—R″—NH₂; wherein R″is independently an optionally substituted hydrocarbyl orhydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3. The optionalsubstituents on R″ can be any heteroatom-containing group that does notparticipate directly in reactions between the substrate polymer and thecrosslinking agent; i.e., the substituent is preferably not displacedduring such reaction and does not form a covalent bond with thesubstrate polymer. Groups attached to the polymer by reaction with G cancontain aza (—NZ-) or ether (—O—) linkages (e.g., G can be PEGylated).

In one embodiment of the process, less than 100% of the reactive pendantgroups are derivatized to make the derivatized pendant groupssubstantially unreactive to the crosslinking agent, wherein thederivatization is performed either before, during or after contact ofthe crosslinker with the polymer substrate. “Substantially unreactive”,as used herein, means having a rate of reaction, e.g., with thecrosslinking agent, of about 20% or less of the rate of reaction of anunderivatized pendant group under the same conditions. Preferably thereactive pendant groups are derivatized to contain an optionallysubstituted aliphatic carbon chain with optional —(NZ)-, and —O—linkages, where Z is hydrogen, optionally substituted alkyl oroptionally substituted aryl.

In another embodiment, the crosslinking agent is derived from an aldaricacid, aldarolactone, aldarodilactone, aldarolactone ester, aldaric acidmonoester, aldaric acid diester, or aldaramide, or salts thereof, andthe substrate polymer comprises polyallylamine, polyallylaminehydrochloride, branched polyethyleneimine, branched polyethyleneiminehydrochloride, poly(acryloyl chloride), poly(methacryloyl chloride),poly[N-(ω-aminoalkyl)acrylamide], polyglycosamine,carboxymethylchitosan, chitosan, chitosan hydrochloride, or derivativesor salts thereof. By “derived from” is meant that the crosslinking agentcan be produced from a starting compound in about six or fewer chemicalreaction steps, and retains an aldaric structure —C(═O)(CHOR)_(n)C(═O)—wherein R is H or a carbon-containing group such as alkyl.

Preferably the crosslinking agent is selected from compounds havingFormulae IX, X, XI, and XII:

wherein A1 is selected from the group consisting of:

and salts thereof;

-   -   and A2 is selected from the group consisting of        —NH—R₅—NH—        —NH—R₅—O—        and        —O—R₅—O—        and salts thereof;    -   wherein R₅ and R₇ are independently aliphatic or aromatic        hydrocarbylene groups, linear, branched or cyclic, optionally        substituted, and optionally containing —O—, —Si(ZZ′)O—, —(C═O)—        or —NZ- linkages, where Z and Z′ are independently hydrogen,        alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl, or        substituted aryl; and R₆ is hydrogen or a 1-22 carbon alkyl        group.

These and other aspects of the present invention will be apparent to oneskilled in the art, in view of the following description and theappended claims.

DETAILED DESCRIPTION

The following definitions may be used for the interpretation of thespecification and the claims:

By hydrocarbyl is meant a straight chain, branched or cyclic arrangementof carbon atoms connected by single, double, or triple carbon-to-carbonbonds, and substituted accordingly with hydrogen atoms. Such hydrocarbylgroups can be aliphatic and/or aromatic. Examples of hydrocarbyl groupsinclude methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl,cyclopropyl, cyclobutyl, cyclopentyl, methylcyclopentyl, cyclohexyl,methylcyclohexyl, benzyl, phenyl, o-tolyl, m-tolyl, p-tolyl, xylyl,vinyl, allyl, butenyl, cyclohexenyl, cyclooctenyl, cyclooctadienyl, andbutynyl. Examples of substituted hydrocarbyl groups include tolyl,chlorobenzyl, —(CH₂)—O—(CH₂)—, fluoroethyl, p-(CH₃S)C₆H₅,2-methoxypropyl, and (CH₃)₃SiCH₂.

“Alkyl” means a saturated hydrocarbyl group. Common examples of suchalkyl groups include methyl, ethyl, propyl, isopropyl, butyl, s-butyl,isobutyl, pentyl, neopentyl, hexyl, heptyl, isoheptyl, 2-ethylhexyl,cyclohexyl and octyl.

“Aryl” means a group defined as a monovalent radical formed conceptuallyby removal of a hydrogen atom from a hydrocarbon that is structurallycomposed entirely of one or more benzene rings. Common examples of suchhydrocarbons include benzene, biphenyl, terphenyl, naphthalene, phenylnaphthalene, and naphthylbenzene.

“Alkaryl” means an alkylated aryl group; that is, an aryl group asdefined above that is substituted with an alkyl group.

By “hydrocarbylene,” “alkylene,” “arylene,” or “alkarylene” is meant thedivalent form of the corresponding group.

“Substituted” and “substituent” mean that a group is substituted andcontains one or more substituent groups, or “substituents,” that do notcause the compound to be unstable or unsuitable for the use or reactionintended. Unless otherwise specified herein, when a group is stated tobe “substituted” or “optionally substituted,” substituent groups thatcan be present include carboxyl, carboxamido (including primary,secondary or tertiary carboxamido), acylamino, alkoxycarbonylamino,sulfonylamino, cyano, alkoxy, alkoxycarbonyl, acyloxy, fluoro, chloro,bromo, iodo, amino (including primary, secondary and tertiary amino),hydroxy, alkenyl, oxo, imino, hydroxyimino, hydrocarbyloxyimino, whereinthe hydrocarbyl group can be aliphatic, aryl or a combination of thetwo, trihydrocarbylsilyl, wherein each hydrocarbyl group can beindependently alkyl or aryl, trihydrocarbylsiloxy, wherein eachhydrocarbyl group can be independently alkyl or aryl, nitro, nitroso,hydrocarbylthio, wherein the hydrocarbyl group can be aliphatic, aryl ora combination of the two, hydrocarbylsulfonyl, wherein the hydrocarbylgroup can be aliphatic, aryl or a combination of the two,hydrocarbylsulfinyl, wherein the hydrocarbyl group can be aliphatic,aryl or a combination of the two, hydrocarbyloxysulfonyl, wherein thehydrocarbyl group can be aliphatic, aryl or a combination of the two,sulfonamido (including primary, secondary and tertiary sulfonamido),sulfonyl, dihydrocarbylphosphino, wherein each hydrocarbyl group can beindependently alkyl or aryl, dihydrocarbyloxyphosphino, wherein eachhydrocarbyl group can be independently alkyl or aryl,hydrocarbylphosphonyl, wherein the hydrocarbyl group can be aliphatic,aryl or a combination of the two, hydrocarbyloxyphosphonyl, wherein thehydrocarbyl group can be aliphatic, aryl or a combination of the two,phosphonamido (including primary, secondary and tertiary phosphonamido),and salts of the aforementioned.

Aldaric acids are diacids derived from naturally occurring sugars. Whenaldoses are exposed to strong oxidizing agents, such as nitric acid,both the aldehydic carbon atom and the carbon bearing the primaryhydroxyl group are oxidized to carboxyl groups. This family of diacidsis known as aldaric acids (or saccharic acids). An aldarolactone has onecarboxylic acid lactonized; the aldarodilactone has both lactonized. Asillustration, the aldaric acid derivatives starting from D-glucose areshown below.

Any stereoisomer or mixture of stereoisomers can be used in theprocesses of the present inventions. The aldaric acid derivative can beglucaric acid or galactaric acid, or their derivatives such asglucarolactone, glucarodilactone, galactarolactone, and dimethylgalactarate.

The invention is directed to processes for preparing crosslinkedpolymers comprising contacting a crosslinking agent with a substratepolymer to form a crosslinked polymer; wherein the crosslinking agent isone or more of Formulae VI, VII and VIII:

and n=1-6, m=0-4, and p=1-4. Preferably n=2-4, m=0-1, and p=2-3.

The substrate polymer used in the instant process comprises a linear,branched or cyclic polymeric backbone. The backbone contains repeatunits that comprise one or more of hydrocarbylene groups, heteroatoms,and carbonyl carbon groups. The hydrocarbylene groups are aliphatic oraromatic, linear, branched, or cyclic, or combinations thereof. Thehydrocarbylene groups and heteroatoms of the repeat units are optionallysubstituted with substituents that comprise one or more of C₁-C₃₀hydrocarbylene groups, heteroatoms, and carbonyl carbon groups, whereinthe hydrocarbylene groups of the substituents are aliphatic or aromatic,linear, branched, or cyclic, or combinations thereof.

The polymeric backbone used in the process can contain —NZ-, —N⁺ZZ′-,—O—, —C(═O)NZ-, —C(═O)O—, —C(═O)—, —OC(═O)O—, —OC(═O)NZ-, —NZC(═O)NZ′-,or —SiZZ′O— linkages, where Z and Z′ are independently hydrogen, alkyl,substituted alkyl, aryl, or substituted aryl.

The substituents on the repeat units are preferably one or more of —X,—O(Z), —N(ZZ′)-, —N⁺(ZZ′Z″), —C(═O)OZ, —C(═O)X, —C(═O)NZZ′, —C═N═O—,—O—, —N(Z)-, —N⁺(ZZ′)-, —C(═O)N(Z)-, —C(═O)O—, —C(═O)—, —OC(═O)O—,—OC(═O)N(Z)-, —N(Z)C(═O)N(Z′)-, —C(═O)NH(CH₂)_(p)NH₂, —Si(ZZ′)O—,—(OCH₂CH₂)_(m)OH, or —(OSi(ZZ′))_(n)OH, or salts thereof, where X is ahalogen, Z, Z′, and Z″ are independently hydrogen, C₁-C₂₂ optionallysubstituted alkyl, or C₁-C₂₂ optionally substituted aryl, and where m is1 to 50, n is 1 to 100, and p is 1 to 12. More preferably, thesubstituents comprise one or more of C₁-C₂₂ aminoalkyl groups,optionally substituted with alkyl or aldaroyl, or a salt thereof. Therepeat units preferably comprise aliphatic hydrocarbylene groups withsubstituents comprising one or more of aminoalkyl groups, —C(═O)OZ,—C(═O)X, —C(═O)NZZ′, or —C(═O)NH(CH₂)_(n)NH₂, or salts thereof, where Xis halogen, Z and Z′ are independently hydrogen, C₁-C₂₂ alkyl,substituted alkyl, aryl, or substituted aryl, and n=1-12.

The repeat unit can be an azahydrocarbylene or a salt thereof with oneor more terminal amino groups or salts thereof as substituents on the Nof the azahydrocarbylene repeat unit.

The substrate can also comprise polyallylamine, polyallylaminehydrochloride, branched polyethyleneimine, branched polyethyleneiminehydrochloride, poly(acryloyl chloride), poly(methacryloyl chloride),poly[N-(ω-aminoalkyl)acrylamide], polyglycosamine,carboxymethylchitosan, chitosan, chitosan hydrochloride, or derivativesor salts thereof.

Attached to the polymeric backbone are reactive pendant groups of theformula -G or —R-G; where G is a nucleophile or electrophile; and whereR is independently linear, cyclic, or branched alkylene, arylene, oralkarylene groups of 1-22 carbon atoms, optionally substituted withalkyl, aryl, hydroxy, amino, carbonyl, ester, amide, alkoxy, nitrile orhalogen, and optionally containing —O—, —Si(ZZ′)O—, —(C═O)— or —NZ-linkages, where Z and Z′ are independently hydrogen, alkyl, substitutedalkyl, alkaryl, substituted alkaryl, aryl, or substituted aryl.

The terms “electrophile” and “nucleophile” are well known to thoseskilled in the art, and can be broadly defined as reactive chemicalmoieties that act as electron acceptors or electron donors. Preferred iswhere G is an epoxide, isocyanate, benzylic halide, amine, acid halide,ester, or amide; more preferred is where G is —NH₂, —C(═O)Cl, —C(═O)OR″or —C(═O)NH—R″—NH₂; wherein R″ is independently hydrogen or anoptionally substituted hydrocarbyl or hydrocarbylene. Most preferably Gis —NH₂.

L and L′ are defined as containing a suitable functional group. Asuitable functional group is herein defined as a functional group thatreadily forms a covalent bond with the reactive pendant group. Thespecific functional group employed will depend upon the particularsynthetic method used to make the crosslinked polymer. It may containheteroatoms such as O, N, S, and/or is derived from a functional groupsuch as an amine, hydroxyl, carboxylic acid, ester, urethane, urea,amide, or isocyanate. Particularly useful functional groups are thosethat contain a —NH— group, a —C(═O)O— group, a —O— group, or saltsthereof. Preferably, the suitable functional group is derived from anamine, hydroxyl, carboxylic acid, ester, urethane, urea, amide, orisocyanate. More preferably L and L′ are independently selected from thegroup consisting of —Y—R, wherein Y is O, NH, or S and R is alkyl,substituted alkyl, alkaryl, substituted alkaryl, aryl, or substitutedaryl. Also more preferably L and L′ are independently selected from thegroup consisting of optionally substituted —NHR″, —OR″, andhydrocarbylene-C(═O)OR″; wherein R″ is an optionally substitutedhydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3.

As illustration, a crosslinker that is capped with a carboxylic acid asthe suitable functional group would be expected to react readily withavailable amine pendant groups on the polymeric backbone. A crosslinkerend-capped with a hydroxyl group or an amine as a functional group wouldnot be expected to react with the pendant amine functionality of thepolymeric backbone. However, if the subject polymer backbone had acarboxylic acid or an isocyanate as pendant functionality, then acrosslinker capped with an amine or a hydroxyl functional group couldreact with the pendant group of the polymeric backbone.

In another embodiment, less than 100%, preferably about 50% or less, andmore preferably about 20% or less, of the reactive pendant groups arederivatized to make the derivatized pendant groups unreactive to thecrosslinking agent. The derivatization can be performed by contactingthe reactive pendant groups with a derivatizing reagent before, duringor after contact of the crosslinker with the polymer substrate.Preferably, the reactive pendant groups are derivatized before thecontact of the crosslinker with the polymer substrate. The reactivependant groups can be derivatized to contain an optionally substitutedaliphatic carbon chain with optional —(NZ)-, and —O— linkages, where Zis hydrogen, optionally substituted alkyl or optionally substitutedaryl. Preferably, the reactive pendant groups are derivatized to containa linear or branched alkyl group of 1-22 carbon atoms, optionallysubstituted with —O— linkages, and optionally substituted with —NH₂,halogen, hydroxyl, or carbonyl groups, or salts thereof; more preferablya C₁-C₂₂ alkyl group, most preferably a C₂-C₁₈ unsubstituted alkylgroup.

The crosslinking agent can be derived from an aldaric acid,aldarolactone, aldarodilactone, aldarolactone ester, aldaric acidmonoester, aldaric acid diester, or aldaramides, or salts thereof.Preferably the crosslinking agent is derived from glucaric acid,galactaric acid, mannaric acid, xylaric acid or tartaric acid.

In another embodiment, the crosslinking agent is of the Formulae IX, X,XI, XII:

wherein A1 is selected from the group consisting of:

and salts thereof; and A2 is selected from the group consisting of—NH—R₅—NH——NH—R₅—O—and—O—R₅—O—and salts thereof. R₅ and R₇ are independently aliphatic or aromatichydrocarbylene groups, linear or cyclic, optionally substituted withalkyl, aryl, hydroxy, amino, carbonyl, carboxyl, ester, amide, alkoxy,nitrile or halogen, or slats thereof, and optionally containing —O—,—Si(ZZ′)O—, —(C═O)— or —NZ- linkages, where Z and Z′ are independentlyhydrogen, alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl,or substituted aryl; and R₆ is hydrogen or a 1-22 carbon alkyl group.

Preferably, R₅ and R₇ are independently optionally substituted aliphaticcarbon chains with optional —(NZ)- or —O— linkages, wherein Z ishydrogen, optionally substituted alkyl or optionally substituted aryl.More preferably, R₅ and R₇ are independently linear, cyclic, or branchedalkylene groups of 1-10 carbon atoms, optionally substituted with —O—linkages, and optionally substituted with —NH₂ groups, or salts thereof.

Also preferably, R₇ is —[(CH₂)₁₋₂₁]—, —CH(CH₃)—, —CH(isopropyl)-,—CH(isobutyl)-, —CH(CH(CH₃)CH₂CH₃)—, —CH(CH₂OH)—, —CH(CH₂CH₂SCH₃)—,—CH(CH(OH)CH₃)—, —CH(CH₂C₆H₅)—, —CH(CH₂C₆H₄OH)—, —CH(CH₂CONH₂)—, or—CH(CH₂CH₂CONH₂)—; and

-   -   R₅ is —[(CH₂)₂₋₂₂]—, —[(CH₂)₀₋₆(C₆H₁₀)(CH₂)₀₋₆]—,        —[(CH₂)₀₋₆C₆H₄(CH₂)₀₋₆]—, —[CH₂CH₂(OCH₂CH₂)₁₋₂₁]—,        —[CH₂CH(CH₃)[OCH₂CH(CH₃)]₁₋₂₁]—, —(CH₂CH₂NH)₁₋₂₂CH₂CH₂—,        —[CH₂CH(CH₃)[OCH₂CH(CH₃)]_(x)(OCH₂CH₂)_(y)[OCH₂CH(CH₃)]_(z) —        wherein x+y+z=2-50,        —[CH₂CH₂(OCH₂CH₂)_(x)[OCH₂CH(CH₃)]_(y)(OCH₂CH₂)_(z)]— wherein        x+y+z=2-50,        —[CH(CH₃)CH₂O]_(x)CH₂C(Z′)(CH₂[OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)—        wherein x+y+z=2-10 and Z′ is H, methyl or ethyl,        —[CH(CH₃)CH₂O]_(x)CH₂CH([OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)—        wherein x+y+z=3-100, or        —CH₂CH₂CH₂CH₂[CH(NH₂)CONHCH₂CH₂CH₂CH₂]₀₋₁₀CH(COYR)— or salts        thereof, wherein Y is O or NH, and R is a C₁-C₂₂ optionally        substituted alkyl, aryl, or alkaryl.

Examples of polyoxaalkyleneamines that can be used include those basedon Jeffamine® polyether amines (Huntsman LLC, Salt Lake City, Utah).Polytetramethylene glycols that can be used include those based onTerathane® polytetramethylene ether glycol (E. I. DuPont de Nemours,Wilmington, Del.).

In some embodiments, about 0.0005 to about 0.5 molar equivalents ofcrosslinking agent per reactive pendant group can be used in theprocess. Preferably, from about 0.005 to about 0.5 molar equivalents ofcrosslinking agent are used per reactive pendant group, and morepreferably about 0.01 to 0.25 molar equivalents per reactive pendantgroup.

The processes can be run at any suitable temperature but preferably atabout 20° C. to about 100° C. The processes can be carried out in apolymer melt, but are preferably carried out in the presence of asolvent. The choice of solvent is not critical provided the solvent isnot detrimental to reactant or product. Preferred solvents includewater, dimethylformamide, dimethylformamide LiCl, dimethylacetamide,dimethylacetamide LiCl, ethanol, and methanol.

The polymers described herein are suitable for use as hydrogels.Hydrogels (hydrated gels) are herein defined as materials that absorblarge quantities of liquid, i.e., greater than 2 mass equivalents ofliquid. They are usually water-swellable, three-dimensional networks ofmacromolecules held together by covalent or noncovalent crosslinks. Whenplaced in aqueous solution, these networks swell to the extent allowedby the degree of crosslinking. Hydrogels are useful in a variety ofapplications, such as medical products, personal care formulations,exfoliants, humectants, surfactants, thickeners, anti-irritants,antimicrobials, lubricants, emulsifiers, delivery agents, coatings, andsurfactants. The crosslinked polymers invention can be modified toproduce a variety of desirable properties for particular applications.

EXAMPLES

Abbreviation Ingredient Name 1BrC16 1-bromohexadecane 4,9-DODDA4,9-dioxa-1,12-dodecanediamine 9DA 1,9-diaminononane DMG dimethylgalactarate GA D-glucaric acid GDL D-glucaro-1,4:6,3-dilactone HMDA1,6-hexanediamine JEFF Jeffamine ® JEFF EDR-148 Jeffamine ®(H₂NCH₂CH₂OCH₂CH₂OCH₂CH₂NH₂) JEFF EDR-192 Jeffamine ®(H₂NCH₂CH₂(OCH₂CH₂)₃NH₂) JEFF T5000 Jeffamine ® polyethertriamine JEFFT403 Jeffamine ® polypropyleneoxytriamine PAlAmHCl polyallylamine HCl(obtained from Polysciences, Inc., Warrington, PA)

Analyses

Unless otherwise specified, the analyses were performed as follows.

Inherent Viscosity (η_(inh))

Inherent viscosities were generally run as 0.5% solutions in eitherhexafluoroisopropanol (HFIP) or m-cresol at 30° C.

Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis(TGA)

DSC and TGA studies of all polymers were conducted on 5-10 mg samplesrun at 10° C./min under nitrogen. Sample temperatures spanned rangesbeginning as low as −100° C. to as high as 300° C., depending on polymercharacter and stability. Samples were generally cooled after the firstheat cycle and a second heat cycle was then conducted. Generally,polymer DSC results reported are second heat results to eliminateartifacts of thermal history variations.

Swell Factor

Into a pre-dried, tared, 150 mL coarse fritted filter funnel was addedabout 1 g of polymer. The stem of the funnel was sealed with a rubberstopper. The funnel was placed on a filter flask and about 100 mL ofdistilled water at about 22° C. is added to the funnel. The contentswere stirred, if necessary, to fully disperse the water and polymer. Thecontents were then left undisturbed for 15 minutes. The rubber stopperwas then removed from the stem of the funnel, and suction was applied tothe funnel for 5 minutes. The stem and underside of the funnel were thenrinsed with ethanol to remove any remaining water droplets and suctionwas then continued for an additional 5 minutes. Any remaining waterdroplets were wiped off the funnel with a paper towel. The funnel andcontents were then weighed to determine the weight of water retained bythe polymer. $\begin{matrix}{{{Swell}\quad{factor}} = \frac{\begin{matrix}{\left( {{{total}\quad{{wt}.\quad{of}}\quad{wet}\quad{polymer}} + {funnel}} \right) -} \\\left( {{{total}\quad{{wt}.\quad{of}}\quad{dry}\quad{polymer}} + {funnel}} \right)\end{matrix}}{{{wt}.\quad{of}}\quad{dry}\quad{polymer}}} \\{= \frac{\left( {{wet}\quad{{wt}.\quad{- {dry}}}\quad{{wt}.}} \right)}{{dry}\quad{{wt}.}}} \\{= \frac{g\quad{water}\quad{retained}}{g\quad{polymer}}}\end{matrix}$

Solubility

Solubilities were generally determined using 0.01 g of test material in10 mL of test solvent. The vials containing the samples were constantlyagitated via a shaker tray at room temperature for anywhere between 24hours and 4 weeks. Solubility was determined by visual inspection todetermine sample homogeneity. Any variance in density gradient, orrefractive index was taken as indicating insolubility. Samples deemed tobe insoluble were shaken at room temperature for at least 1 week, and inmany cases were shaken for 2 weeks or more. A wide range of commonsolvent types was generally used to allow a broad range of polarity andsolvent parameters to come into play.

Film Properties

Film properties were determined on 0.25 in×2 in samples cut from largerfilms spread onto glass with a blade applicator. Generally, films hadthicknesses of 5 mil or less. Film properties reported represent anaverage of at least five measurements for each sample.

The reactions depicted in the following Examples are meant to beillustrative only and not representative of exact structures.

Examples 1-28

Polymers were prepared by first dissolving polyallylamine hydrochlorideof ˜60,000 molecular weight in water. To that solution was added enoughsodium hydroxide to just neutralize the equivalent amount of ammoniumhydrochloride functions as would be used by the added GDL. To thepartially neutralized polyallylamine hydrochloride was added a watersolution of GDL at room temperature. The reaction was substantially overin a matter of minutes. A representative polymerization with GDL isshown below.

The crosslinking was performed using various compounds as describedbelow in a representative reaction with GDL. When another compound wasused in the in the crosslinking reaction along with the GDL, such as9DA, they were both added simultaneously. Into a 250-mL 3-necked roundbottom flask equipped with a heating mantle, reflux condenser, nitrogeninlet, and overhead stirrer was added 20 mL of water, 2.80 g (0.030equivalent, 60,000 MW) of polyallylamine HCl, and 0.26 g (0.0066 mol) ofsodium hydroxide. This mixture was stirred at room temperature until ahomogeneous solution was achieved (˜10 minutes). At this point, ahomogeneous solution prepared from 10 mL of water and 0.57 g (0.0033mol) of GDL was slowly poured at room temperature into the solutioncontaining the polyallylamine HCl. Within 1 to 2 minutes, gel hadformed. The gel was then allowed to stir for ˜2 hours at roomtemperature, after which time it was removed from the flask. The gel wasthen washed 3 times with 100 mL aliquots of methanol followed by THF.The gel was then dried in a vacuum oven at 80° C. to yield 2.79 g(89.1%) of a granular white hydrogel polymer. The results are shown inTable 1. The % crosslinking shown in Table 1 is a theoreticalcalculation of the % of total amine nitrogens (from the polyallylaminehydrochloride) tied up in the crosslinking process with the aldaricacid. The calculation was based on the total weight of polyallylaminehydrochloride used (molar equivalents of allylamine) and the total molarequivalents of the GDL added to the process. Total final crosslinkingwas not measured but is assumed since the polymer gelled and becameinsoluble, although NMR indicated that conversion was less than 100%.

When only 5-15% of the ammonium groups were allowed to react with GDL, avery viscous water solution resulted that could be cast into a film. Theresulting films were brittle, but less so than the startingpolyallylamine hydrochloride homopolymer. As more ammonium groupsreacted with GDL, gels eventually formed. Highly swellable hydrogels(with swell ratios as high as 90) were readily formed when ˜22% of theammonium hydrochloride equivalents were neutralized and GDL was added inan equivalent amount (˜11% since both ends of the molecule are assumedto react). The gels were optically clear and colorless. It is unknown asto how much of the GDL was fully incorporated into the polymer, but itdoes appear that an equilibrium was reached in the polymer as evidencedby hydrogel samples that had been kept in water for months withoutloosing viscosity. If hydrolysis fully destroys all of the initiallyformed amide bonds, the hydrogel would slowly lose viscosity andeventually fully dissolve.

The data in Tables 1 and 2 show some of the properties that can beobtained in the polymers by varying the ingredients used in making them.TABLE 1 Solvent/ % Ex. Composition Catalyst Media Color Yield Inh ViscInh Sol. Polym. Character Swell 1 PAlAmHCl/GDL (10:1) - 20%triethylamine water white — insol HFIP Powder 4.72 crosslinking 2PAlAmHCl/GDL (8:1) - 25% triethylamine water white — insol HFIP powder -very brittle 12.27 crosslinking film 3 PAlAmHCl/GDL (8.7:1) - 23%triethylamine water white — insol HFIP powder - poor film 80.73crosslinking 4 PAlAmHCl/GDL (5:1) - 40% triethylamine water off white90.1 insol HFIP Powder 48 crosslinking 5 PAlAmHCl/GDL (9.1:1) - 22%triethylamine water white — insol HFIP powder - very brittle 28.1crosslinking film 6 PAlAmHCl/GDL (9.1:1) - 22% sodium water white 89.1insol HFIP Powder 89.5 crosslinking hydroxide 7 PAlAmHCl/GDL (9.1:1) -22% calcium water white 84.7 insol HFIP Powder 88.5 crosslinkinghydroxide 8 PAlAmHCl/GDL (9.1:1) - 22% calcium water white — insol HFIPpowder - poor film, 6.36 crosslinking hydroxide very brittle 9PAlAmHCl/GDL (9.1:1) - 22% calcium water white — insol HFIP powder -poor film, sol. in crosslinking hydroxide very brittle water 10PAlAmHCl/(GDL/JEFF EDR- sodium water white 68.1 insol water powder -brittle, clear 71.3 148 (2:1)) - 20% crosslinking hydroxide film 11PAlAmHCl/(GDL/JEFF EDR- sodium water white 92.9 insol water powder -brittle, clear 49 192 (2:1)) - 20% crosslinking hydroxide film 12PAlAmHCl/(GDL/JEFF T5000 sodium water/ white 40   insol water Powder40.1 (3:1)) - 10% crosslinking hydroxide ethanol 13 PAlAmHCl/(GDL/JEFFT5000 sodium water/ white 31.9 insol water Powder 8.04 (3:1)) - 20%crosslinking hydroxide ethanol 14 PAlAmHCl/(GDL/JEFF T5000 sodium water/white 28.4 insol water powder - poor film sol. in (3:1)) - 5%crosslinking hydroxide ethanol water 15 PAlAmHCl/(GDL/JEFF T5000 sodiumwater/ white — insol water powder - poor, clear, sol. in (3:1)) - 1%crosslinking hydroxide ethanol brittle film water 16 PAlAmHCl/(GDL/JEFFT5000 sodium water/ white 61.6 insol water powder - very poor 11(3:1)) - 3% crosslinking hydroxide ethanol film 17 PAlAmHCl/(GDL/JEFFT403 sodium water white 69.4 insol water powder - poor, brittle sol.in(3:1)) - 3% crosslinking hydroxide film water 18 PAlAmHCl/(GDL/JEFF T403sodium water white 74.2 insol water powder - poor, very sol. in (3:1)) -5% crosslinking hydroxide brittle film water 19 PAlAmHCl/(GDL/JEFF T403sodium water white 83.9 insol water powder - poor, brittle 83.8 (3:1)) -20% crosslinking hydroxide film 20 PAlAmHCl/(GDL/4,9-DODDA sodium waterwhite 77.4 insol water powder - clear film, 78.6 (2:1)) - 20%crosslinking hydroxide slightly flexible, fair 21PAlAmHCl/(GDL/4,9-DODDA sodium water light 77.2 insol water powder -very poor 26.7 (2:1)) - 25% crosslinking hydroxide yellow film 22PAlAmHCl/(GDL/(9DA/4,9- sodium water white 60   — — Powder 31.1 DODDA)(2:0.5:0.5)) - 20% hydroxide crosslinking 23 PAlAmHCl/(GDL/9DA (2:1)) -sodium water white 63.6 — — Powder 23.7 20% crosslinking hydroxide 24PAlAmHCl/(GDL/9DA (2:1)) - sodium water white — — — powder - fair film,75.2 15% crosslinking hydroxide slightly flexible 25 PAlAmHCl/(GDL/4,9-sodium water tan — — — powder - poor, brittle 48.5 DODDA/9DA(2/0.5/0.5)) - 15% hydroxide film crosslinking 26PAlAmHCl/(GDL/4,9-DODDA sodium water tan — — — powder - poor film 2(1.33:1)) hydroxide 27 PAlAmHCl/(GDL/9DA (1.33:1)) sodium water offwhite — — — powder - poor film 1.29 hydroxide 28 PAlAmHCl/(GDL/9DA(2:1)) - sodium water light 82.9 — — Powder 0.65 100% crosslinkinghydroxide yellow

TABLE 2 Ex. Composition Tg 1 (C) Tg 2 (C) Tg 3 (C) Tm 1 (C) ΔH (J/g) Tm2 (C) d H (J/g) Tm 3 (C) d H (J/g) 1 PAlAmHCl/GDL (10:1) - — — — 180.9 — — — — — 20% crosslinking 2 PAlAmHCl/GDL (8:1) - 25% — — — 190.97 — — —— — crosslinking 3 PAlAmHCl/GDL (8.7:1) - — — — 191.23 7.544 — — — — 23%crosslinking 4 PAlAmHCl/GDL (5:1) - 40% — — — 192.38 17.99 — — — —crosslinking 5 PAlAmHCl/GDL (9.1:1) - — — — 196.63 5.076 — — — — 22%crosslinking 6 PAlAmHCl/GDL (9.1:1) - — — — 196.75 5.318 — — — — 22%crosslinking 7 PAlAmHCl/GDL (9.1:1) - — — — 251.32 15.99 — — — — 22%crosslinking 8 PAlAmHCl/GDL (9.1:1) - — — — 202.61 7.165 — — — — 22%crosslinking 9 PAlAmHCl/GDL (9.1:1) - — — — 165.56 1.245 — — — — 22%crosslinking 10 PAlAmHCl/(GDL/JEFF — — — 187   5.99 248.04 6.291 — —EDR-148 (2:1)) - 20% crosslinking 11 PAlAmHCl/(GDL/JEFF — — — — — — — —— EDR-192 (2:1)) - 20% crosslinking 12 PAlAmHCl/(GDL/JEFF — — — 188.451.008 251.86 4.542 — — T5000 (3:1)) - 10% crosslinking 13PAlAmHCl/(GDL/JEFF — — — 251.88 7.862 — — — — T5000 (3:1)) - 20%crosslinking 14 PAlAmHCl/(GDL/JEFF — — — 220.09 2.666 — — — — T5000(3:1)) - 5% crosslinking 15 PAlAmHCl/(GDL/JEFF 204.2 — — — — — — — —T5000 (3:1)) - 1% crosslinking 16 PAlAmHCl/(GDL/JEFF 102.6 215.5 — — — —— — — T5000 (3:1)) - 3% crosslinking 17 PAlAmHCl/(GDL/JEFF 224.4 — — — —— — — — T403 (3:1)) - 3% crosslinking 18 PAlAmHCl/(GDL/JEFF 170   232.3— — — — — — — T403 (3:1)) - 5% crosslinking 19 PAlAmHCl/(GDL/JEFF 175.7227.5 — — — — — — — T403 (3:1)) - 20% crosslinking 20 PAlAmHCl/(GDL/4,9-168.8 234.4 204.7 1.281 — — — — DODDA (2:1)) - 20% crosslinking 21PAlAmHCl/(GDL/4,9- 171   209.5 247.6 — — — — — — DODDA (2:1)) - 25%crosslinking 22 PAlAmHCl/(GDL/(9DA/4,9- 174.4 — — — — — — — — DODDA)(2:0.5:0.5)) - 20% crosslinking 23 PAlAmHCl/(GDL/9DA 174.9 — — — — — — —— (2:1)) - 20% crosslinking 24 PAlAmHCl/(GDL/9DA 168.7 — — — — — — — —(2:1)) - 15% crosslinking 25 PAlAmHCl/(GDL/4,9- 142.5 174.2 — 224.280.261 — — — — DODDA/9DA (2/0.5/0.5)) - 15% crosslinking 26PAlAmHCl/(GDL/4,9-  45   216.6 — 103.33 177.97 23.69 188.41 16.3   DODDA(1.33:1)) 27 PAlAmHCl/(GDL/9DA  75.94 — — 152.48 12.17 165.25 31.69195.55  9.072 (1.33:1)) 28 PAlAmHCl/(GDL/9DA (2:1)) - — — — 167.03 4.206190.61 14.02 — — 100% crosslinking

TABLE 3 Tc 1 d H Tc Tdec Sol. Sol. Sol. Sol. Sol. Sol. Sol. Ex.Composition (C) (J/g) 2 (C) d H (J/g) (C) H2O MeOH Toluene DMSO DMAC THFCH2CL2 1 PAlAmHCl/GDL (10:1) - — — — — 200 sol. insol. insol. insol.insol. insol. insol. 20% crosslinking 2 PAlAmHCl/GDL (8:1) - 25% — — — —200 insol. insol. insol. insol. insol. insol. insol. crosslinking 3PAlAmHCl/GDL (8.7:1) - — — — — 225 insol. insol. insol. insol. insol.insol. insol. 23% crosslinking 4 PAlAmHCl/GDL (5:1) - 40% — — — — 225insol. insol. insol. insol. insol. insol. insol. crosslinking 5PAlAmHCl/GDL (9.1:1) - — — — — 200 insol. insol. insol. insol. insol.insol. insol. 22% crosslinking 6 PAlAmHCl/GDL (9.1:1) - — — — — 225insol. insol. insol. insol. insol. insol. insol. 22% crosslinking 7PAlAmHCl/GDL (9.1:1) - — — — — 220 insol. insol. insol. insol. insol.insol. insol. 22% crosslinking 8 PAlAmHCl/GDL (9.1:1) - — — — — 210insol. insol. insol. insol. insol. insol. insol. 22% crosslinking 9PAlAmHCl/GDL (9.1:1) - — — — — 210 sol. insol. insol. insol. insol.insol. insol. 22% crosslinking 10 PAlAmHCl/(GDL/JEFF — — — — 210 — — — —— — — EDR-148 (2:1)) - 20% crosslinking 11 PAlAmHCl/(GDL/JEFF 223.419.953 — — 210 insol. insol. insol. insol. insol. insol. insol. EDR-192(2:1)) - 20% crosslinking 12 PAlAmHCl/(GDL/JEFF — — — — 200 insol.insol. insol. insol. insol. insol. insol. T5000 (3:1)) - 10%crosslinking 13 PAlAmHCl/(GDL/JEFF — — — — 210 insol. insol. insol.insol. insol. insol. insol. T5000 (3:1)) - 20% crosslinking 14PAlAmHCl/(GDL/JEFF — — — — 225 insol. insol. insol. insol. insol. insol.insol. T5000 (3:1)) - 5% crosslinking 15 PAlAmHCl/(GDL/JEFF — — — — 250sol. insol. insol. insol. insol. insol. insol. T5000 (3:1)) - 1%crosslinking 16 PAlAmHCl/(GDL/JEFF — — — — 235 insol. insol. insol.insol. insol. insol. insol. T5000 (3:1)) - 3% crosslinking 17PAlAmHCl/(GDL/JEFF — — — — 240 sol. insol. insol. insol. insol. insol.insol. T403 (3:1)) - 3% crosslinking 18 PAlAmHCl/(GDL/JEFF — — — — 240sol. insol. insol. insol. insol. insol. insol. T403 (3:1)) - 5%crosslinking 19 PAlAmHCl/(GDL/JEFF — — — — 225 insol. insol. insol.insol. insol. insol. insol. T403 (3:1)) - 20% crosslinking 20PAlAmHCl/(GDL/4,9- — — — — 200 insol. insol. insol. insol. insol. insol.insol. DODDA (2:1)) - 20% crosslinking 21 PAlAmHCl/(GDL/4,9- 284.771.116 — — 200 insol. insol. insol. insol. insol. insol. insol. DODDA(2:1)) - 25% crosslinking 22 PAlAmHCl/(GDL/(9DA/4,9- — — — — 225 insol.insol. insol. insol. insol. insol. insol. DODDA) (2:0.5:0.5)) - 20%crosslinking 23 PAlAmHCl/(GDL/9DA — — — — 225 insol. insol. insol.insol. insol. insol. insol. (2:1)) - 20% crosslinking 24PAlAmHCl/(GDL/9DA — — — — 225 insol. insol. insol. insol. insol. insol.insol. (2:1)) - 15% crosslinking 25 PAlAmHCl/(GDL/4,9- — — — — 175insol. insol. insol. insol. insol. insol. insol. DODDA/9DA(2/0.5/0.5)) - 15% crosslinking 26 PAlAmHCl/(GDL/4,9- — — — — 150 insol.insol. insol. insol. insol. insol. insol. DODDA (1.33:1)) 27PAlAmHCl/(GDL/9DA — — — — 150 insol. insol. insol. insol. insol. insol.insol. (1.33:1)) 28 PAlAmHCl/(GDL/9DA (2:1)) - — — — — 150 — — — — — — —100% crosslinking

Example 29 Synthesis of Modified Polyallylamine Crosslinked with GDL

Into a 2000-mL 3-necked flask equipped with a heating mantle, refluxcondenser, nitrogen inlet, and overhead stirrer was added 525 mL ofwater, 70 g of polyallylamine hydrochloride (0.749 mole equivalent ofamine), and 2.24 g (0.056 mol) of sodium hydroxide. After theseingredients dissolved, 17.08 g (0.056 mol) of 1-bromohexadecane wasadded. The reaction mixture was heated at reflux for 5 hours. Afterward,the reaction mixture was cooled to room temperature and stirredovernight. An additional 5.60 g (0.140 mol) of sodium hydroxide wasadded to the mixture. After the sodium hydroxide dissolved, 12.18 g(0.070 mol) of GDL dissolved in 175 mL of water was added to thereaction mixture. Almost immediately a gel formed. The gelled mixturewas then gently heated at 50° C. for about 7 hours. The gel wasfiltered, washed 3× with methanol, and then washed 3× with THF. It wasthen put into a vacuum oven set at 80° C. for at 24 hours to dry thepolymer. The pale yellow polymer (58.85 g, 60.5%) exhibited a swellratio of 7.9.

Example 30A Synthesis of Polyallylamine Crosslinked with DiethylTartrate

The preparation was conducted under nitrogen atmosphere with oven-driedglassware. Polyallylamine hydrochloride (MW ca. 60,000, 0.876 g, 9.36mmol) was weighed into a 20-mL scintillation vial equipped with amagnetic stirbar, and water (2 mL) was added. Dropwise addition of anaqueous solution (1.0 mL) of sodium hydroxide (0.113 g, 2.83 mmol) tothe solution resulted in a viscous solution. A solution of diethylL-tartrate (0.240 mL, 1.40 mmol) in water (1.0 mL) was added and theresulting solution was stirred at ambient temperatures for 38 hours. Thegelled reaction mixture was washed with methanol (160 mL) to removesodium chloride. Vacuum-drying gave a white solid (0.86 g, 93% yield)that exhibited a swell ratio of 112.6 (determined after swollen gel wassubjected to 6 hours of dynamic suction followed by ˜28 hours of staticsuction).

Example 30B Synthesis of Polyallylamine Crosslinked with DiethylTartrate

Poly(allylamine hydrochloride), M_(w) 60,000 (42.04 g, 0.4493 mole ofamine groups) was dissolved overnight in 155 mL of water in a 3-neck500-mL round-bottom flask equipped with a magnetic stir bar. A solutionof 5.392 g (0.1348 mole) of sodium hydroxide in 25 mL of water was addeddropwise over a period of 10 minutes, using 2 mL of water to completethe transfer. To the resulting pale yellow syrup was added with stirringa solution of 13.897 g (67.40 mmoles) of diethyl L-tartrate in 10 mL ofwater, using 2 mL of water to complete the transfer. The reaction wasallowed to proceed for 4 days, during which the mixture gelled and themagnetic stir bar seized. The reaction mixture was combined with 250 mLof methanol to precipitate out the product. The resulting gummy solidwas separated from the liquid and triturated in a blender with 8successive 250-mL portions of methanol, decanting the methanol eachtime. The resulting solid was ground and dried under vacuum to give38.47g (86% yield) of hydrogel that exhibited a swell factor of 224.

Example 31 Synthesis of Polyallylamine Crosslinked with GDL

The preparation was conducted in a drybox with oven-dried glassware.Polyallylamine hydrochloride (MW ca. 60,000, 6.88 g, 73.5 mmol) wasweighed into a 500-mL round-bottom flask equipped with a magneticstirbar. Methanol (285 mL) was added and the solution was treated withneat triethylamine (12.3 mL, 88.3 mmol) followed by dropwise addition ofa solution of GDL (0.13 g, 0.74 mmol) in methanol (10 mL). The resultingsolution was stirred at ambient temperature for four days. Most of thereaction solvent was decanted, and the remaining reaction mixture wasfiltered and vacuum-dried to give a white solid (1.00 g, 23% yield) thatexhibited a swell ratio of 22.8. When the swell test was repeated,allowing 19 hours for the gel to swell followed by 2 hours of dynamicsuction and 9 hours of static suction, the swell ratio was 22.4. After14 hours' exposure to ambient atmosphere, the sample retained 19.9 timesits own weight in water.

Example 32A Synthesis of Polyallylamine Crosslinked withN,N′-Bis(ethoxycarbonylmethyl)-D-glucaramide

Preparation was conducted in a drybox with oven-dried glassware.Polyallylamine hydrochloride (MW ca. 60,000, 6.55 g, 70.0 mmol) wasweighed into a 500-mL round-bottom flask equipped with a magneticstirbar. Methanol (270 mL) was added and the solution was treated withneat triethylamine (11.7 mL, 84.0 mmol) followed by a slurry ofN,N′-bis(methoxycarbonylmethyl)-D-glucaramide (0.25 g, 0.69 mmol) inmethanol (20 mL). The resulting solution was stirred at ambienttemperature for four days. The reaction solvent was removed undervacuum, and the oily solid was washed repeatedly with methanol (180 mL).Addition of pentane (50 mL) to a methanol slurry (ca. 20 mL volume)produced a solid that was filtered and then vacuum-dried to give a whitesolid (2.39 g, 57% yield) that exhibited a swell ratio (after 29 minutesof suction) of 62.8. When the swell test was repeated, allowing 16 hoursfor the gel to swell followed by 34 minutes of suction, the swell ratiowas 118.9. After 23 hours' exposure to ambient atmosphere, the sampleretained 108.6 times its own weight in water.

Example 32B Synthesis of Polyallylamine Crosslinked withN,N′-Bis(ethoxycarbonylmethyl)-D-glucaramide

To 23.03 g (0.2463 mole of amine groups) of poly(allylaminehydrochloride), Mw 60,000, in 950 mL of dry methanol in a 2-Lround-bottom flask under nitrogen were added 41.2 mL (0.296 mole) oftriethylamine over 30 minutes. A slurry ofN,N′-bis(ethoxycarbonylmethyl)-D-glucaramide in a total of 65 mL of drymethanol was then added. The mixture was stirred at ambient temperaturefor 5 days and then concentrated under reduced pressure to about 150 mL.The resulting solid was separated from the methanol, washed repeatedlywith methanol and then dried under vacuum to give 12.92 g (88% yield) ofhydrogel that exhibited a swell factor of 125.

Example 33

Polyallylamine hydrochloride (MW ca. 60,000, 2.84 g, 30.4 mmol) wasweighed into 100-mL round-bottom flask equipped with a magnetic stirbar.Water (16 mL) was added and the solution was treated with an aqueous (4mL) solution of sodium hydroxide (0.27 g, 6.67 mmol) followed by asolution of GDL (0.58 g, 3.34 mmol) in water (10 mL). The reactionsolution was stirred overnight at ambient temperature resulting in agel-like mixture. The gel was washed with four 50-mL portions ofmethanol and then vacuum-dried to give a white solid (2.26 g, 69% yield)that exhibited a swell ratio (after 2 hours of suction) of 186.5. After3 additional days' exposure to static suction, the sample retained 67.9times its own weight in water. When the swell test was repeated with thesame sample, allowing 5 hours for the gel to swell followed by 2 hoursof dynamic suction and 24 hours of static suction, the swell ratio was206.0. After 3 and 8 days' additional exposure to static suction, thesample retained 173.8 and 65.5 times its own weight in water,respectively.

Example 34

Preparation was conducted under nitrogen atmosphere with oven-driedglassware. Polyallylamine hydrochloride (MW ca. 60,000, 1.01 g, 10.8mmol) was weighed into a 20-mL scintillation vial equipped with amagnetic stirbar, and water (2 mL) was added. Dropwise addition to theslurry of an aqueous solution (1.0 mL) of sodium hydroxide (0.033 g,0.83 mmol) resulted in a viscous solution. A solution ofN,N′-bis(methoxycarbonylmethyl)-D-glucaramide (0.14 g, 0.41 mmol) inwater (1.5 mL) was added, and the resulting solution was stirred atambient temperature for 45 hours. Solvent was removed under vacuum fromthe gelled reaction mixture, and the solid was washed with methanol (125mL) to remove sodium chloride. Vacuum-drying gave a white solid (0.98 g,89% yield) that exhibited a swell ratio (after 5 minutes of dynamicsuction and 45 minutes of static suction) of 105.8. After 2 days'exposure to ambient atmosphere, the sample retained 96.5 times its ownweight in water. When the swell test was repeated with the same sample,allowing 4.5 hours for the gel to swell followed by 5 hours of dynamicsuction and 14 hours of static suction, the swell ratio was 197.6. After6 days' exposure to ambient atmosphere, the sample retained 167.8 timesits own weight in water.

Example 35

Polyethyleneimine (M_(n)=ca. 10,000, M_(w)=ca. 25,000, Aldrich 408727,0.74 g, 17.2 mmol) was weighed into a 20-mL scintillation vial equippedwith a magnetic stirbar, and methanol (4.5 mL) was added. Concentratedhydrochloric acid (0.72 mL, 8.65 mmol) was added to the reactionsolution dropwise over ca. one minute and the mixture was stirred atambient temperature for 3 hours. A solution of GDL (0.15 g, 0.862 mmol)in methanol (1 mL) was added dropwise over ca. one minute to thereaction solution. The reaction mixture began to gel after 3 hours, butstirring was continued for 24 hours. The solvent was removed undervacuum and the solid was vacuum-dried to give a yellow solid (ca. 0.2 g)that exhibited a swell ratio (after 1 hour of static suction) of 24.1.After 5 days' exposure to ambient atmosphere, the sample retained 9.2times its own weight in water. When the swell test was repeated with thesame sample, allowing 7.5 hours for the gel to swell followed by 35minutes of dynamic suction, the swell ratio was 36.6. After 1 day'sexposure to ambient atmosphere, the sample retained 34.2 times its ownweight in water.

Example 36

Polyethyleneimine (M_(n)=ca. 10,000, M_(w)=ca. 25,000, Aldrich 408727,0.67 g, 15.6 mmol) was weighed into a 20-mL scintillation vial equippedwith a magnetic stirbar, and water (2.5 mL) was added. Concentratedhydrochloric acid (0.65 mL) was added dropwise to the solution followedby solid N,N′-bis(methoxycarbonylmethyl)-D-glucaramide (0.14 g, 0.39mmol) and water (1 mL). The reaction solution was stirred for 5 days atambient temperature. The solvent was then removed under vacuum, and thesolid was vacuum-dried to give a colorless solid that exhibited a swellratio (after 50 minutes of dynamic suction and 15 minutes of staticsuction) of 17.6. When the swell test was repeated with the same sample,allowing 15 hours for the gel to swell followed by 2.25 hours ofsuction, the swell ratio was 25.5. After five days' exposure to ambientatmosphere, the sample retained 22.8 times its own weight in water.

Example 37 Biocidal Activity of Crosslinked Hydrogels

Antimicrobial activity was determined by a standard micro-shake flasktest. Bacterial cultures were inoculated into TSB (Trypticase Soy Broth)and incubated at 37° C. overnight for 20±2 hours. The following day, theconcentration of bacteria was adjusted to ˜1.0×10⁵ cfu/mL (cfu=colonyforming unit) by dilution with 0.6 mM phosphate buffer. Dilutedbacterial culture (2.5 mL) was then transferred into culture plate wellscontaining 2.5 mL of hydrogel (˜50 mg of solid dispersed in 2.5 mL of0.6 mM phosphate buffer) or just 2.5 mL of 0.6 mM phosphate buffer(control). The culture plates were incubated at room temperature on aplatform shaker with constant shaking motion. Three 100-μL aliquots wereperiodically removed from each well and serially diluted with 0.6 mMphosphate buffer. Undiluted and diluted samples from each well wereplated onto duplicate TSA (trypticase soy agar) plates, and incubated at37° C. for 20±2 hrs. After incubation, the number of bacterial colonieson each plate was counted using a Q-count instrument or equivalentcounting method. The colony count was averaged and normalized bycorrecting for the dilution factor and reported as the number of colonyforming units (cfu) per mL. Log reduction (log rdxn)=(mean log₁₀ densityof microbes in flasks of untreated control samples)−(mean log₁₀ densityof microbes in flasks of treated samples).

Microbes tested were Escherichia coli, Pseudomonas aeruginosa,Stapphylococcus aureus, and Candida albicans.

Three hydrogel samples were tested for antimicrobial activity: 20 SampleA was prepared as in Example 29. Sample B was prepared as in Example30A. Sample C was prepared as in Example 31. Results are in Table 4.TABLE 4 Biocidal Activity of Crosslinked Hydrogels sample inoculum(control) A B C microbe t, h wt % log cfu log cfu log rdxn log cfu logrdxn log cfu log rdxn E. coli 4 1.0 4.86 1.37 3.49 0.00 4.86 0.00 4.860.50 4.86 1.73 3.13 0.00 4.86 0.00 4.86 0.25 4.86 1.70 3.16 0.00 4.860.00 4.86 0.10 4.86 2.22 2.64 0.00 4.86 0.00 4.86 24 1.0 4.86 0.00 4.860.50 4.86 0.00 4.86 0.25 4.86 0.00 4.86 0.10 4.86 0.00 4.86 P.aeruginosa 4 1.0 4.86 0.00 4.86 0.00 4.86 0.00 4.86 0.50 4.86 0.00 4.860.00 4.86 0.00 4.86 0.25 4.86 0.00 4.86 0.00 4.86 0.00 4.86 0.10 4.860.00 4.86 0.00 4.86 0.00 4.86 S. aureus 4 1.0 4.66 3.94 0.72 0.00 4.660.00 4.66 0.50 4.66 3.92 0.74 0.00 4.66 0.00 4.66 0.25 4.66 3.51 1.150.00 4.66 0.00 4.66 0.10 4.66 3.47 1.19 0.00 4.66 0.00 4.66 24 1.0 4.662.40 2.26 0.50 4.66 1.37 3.29 0.25 4.66 1.18 3.49 0.10 4.66 1.67 2.99 C.albicans 4 1.0 5.09 0.00 5.09 0.00 5.09 0.00 5.09 0.50 5.09 0.00 5.090.00 5.09 0.00 5.09 0.25 5.09 0.00 5.09 0.00 5.09 0.00 5.09 0.10 5.091.92 3.17 0.00 5.09 0.00 5.09

Example 38 Emulsion Prepared Using Hydrogel Prepared from PolvallylamineHCl, GDL, and Jeffamine® EDR-192

A crosslinked hydrogel was prepared in the following manner: 28.0 g(0.30 equiv) of polyallylamine hydrochloride was dissolved in 200 mL ofwater along with 2.4 g (0.06 mol) of sodium hydroxide. To that solutionwas added a solution of 5.2 g (0.030 mol) of GDL and 2.9 g (0.015 mol)of Jeffamine® EDR-192 dissolved in 100 mL of water. The mixture was thenheated to 50° C. Within 1 hour, a gelled product had formed. The gel wasleft to “cure” overnight at room temperature. It was then filtered andwashed 3 times with MeOH/THF. The remaining polymer was then dried in avacuum oven at 80° C. to yield 20.63 g (61%) of a white granularmaterial. The polymer exhibited a swell ratio of 81.

An emulsion was prepared using 2.0 g of the polymer prepared above, 17.0g of octyl palmitate, and 148 mL of water. These ingredients were addedto a 250-mL beaker and emulsified using a Silverson Lab Mixer equippedwith a rotor-stator square-holed blade running at 5,000 rpm for 5 min. Athick, creamy white emulsion was prepared. After 8 months' storage in ajar at room temperature, separation of the emulsion was negligible.

Example 39 Preparation of Crosslinked Polymer using Poly(methacryloylchloride), GDL, and Ethylenediamine

Into a 250-mL 3-necked round-bottom flask equipped with a heatingmantle, reflux condenser, nitrogen inlet, and overhead stirrer was addeda 25 mL of dioxane containing 6.25 g (0.598 equivalent) ofpoly(methacryloyl chloride) (Polysciences, Inc., Warrington, Pa.). Tothis solution was added 3.5 g (0.0150 mol) ofN,N′-bis(2-aminoethyl)-D-glucaramide (prepared by reacting 10equivalents of ethylenediamine with GDL in DMAC at 50° C. and isolatingthe product as a white precipitate). The mixture was stirred and heatedat 50° C. over a period of 21 hours. During this time, a slight colorchange from brown to yellow was noted; however, it did not appear thatthe diaminodiamide was ever fully solubilized in the dioxane solvent.The resulting product was poured into THF, filtered, and washed 3 timeswith THF to yield 2.65 g (27%) of a light tan solid material; Tg₁ 49.67°C.; Tg₂ 64.14° C.; T_(dec) 175° C.-onset; η_(inh) (HFIP) insol.

Example 40 Synthesis of Chitosan Crosslinked with GDL

Chitosan (Primex TM-656, MW ca. 79,000, 95% deacetylated, 0.79 g, 4.90mmol) was weighed into a 20-mL scintillation vial equipped with amagnetic stirbar. Water (11.5 mL) was added, and the mixture was stirredfor 15 minutes at ambient temperature. A solution of hydrochloric acid(37%, 0.29 mL, 3.45 mmol) in water (1.5 mL) was added dropwise, and theresulting viscous light yellow mixture was stirred for 15 minutes atambient temperature. A freshly prepared solution of GDL (0.09 g, 5.40mmol) in water (1.5 mL) was added dropwise, and the reaction mixture wasstirred for 38 hours at ambient temperature, resulting in a tan-coloredhomogeneous gel-like mixture. Approximately 5 mL of the solvent wasremoved under vacuum and the reaction mixture was transferred to around-bottom flask with 15 mL of tetrahydrofuran. The resultingprecipitate was washed with four 30-mL portions of tetrahydrofuran thenvacuum-dried to give a white solid (0.75 g) that had a swell ratio of 3.

1. A process for preparing a crosslinked polymer comprising contacting acrosslinking agent with a substrate polymer to form a crosslinkedpolymer; wherein the crosslinking agent is of Formulae VI, VII or VIII:

wherein L and L′ independently contain a suitable functional group, andn=1-6, m=0-4, and p=1-4; and the substrate polymer comprises: A) alinear, branched or cyclic polymeric backbone comprising repeat unitsthat comprise one or more of hydrocarbylene groups, heteroatoms, andcarbonyl carbon groups; wherein the hydrocarbylene are aliphatic oraromatic, linear, branched, or cyclic, or combinations thereof; andwherein the hydrocarbylene groups and heteroatoms of the repeat unitsare optionally substituted with substituents that comprise one or moreof C₁-C₃₀ hydrocarbylene groups, heteroatoms, and carbonyl carbongroups, wherein the hydrocarbylene groups of the substituents arealiphatic or aromatic, linear, branched, or cyclic, or combinationsthereof; and B) reactive pendant groups attached to the polymericbackbone, the pendant groups being of the formula -G or —R-G, wherein Gis a nucleophile or electrophile; wherein R is independently linear,cyclic, or branched alkylene, arylene, or alkarylene groups of 1-22carbon atoms, optionally substituted with alkyl, aryl, hydroxy, amino,carbonyl, ester, amide, alkoxy, nitrile or halogen, and optionallycontaining —O—, —Si(ZZ′)O—, —(C═O)— or —NZ- linkages, where Z and Z′ areindependently hydrogen, alkyl, substituted alkyl, alkaryl, substitutedalkaryl, aryl, or substituted aryl.
 2. The process of claim 1 whereinthe suitable functional group is derived from an amine, hydroxyl,carboxylic acid, ester, urethane, urea, amide, or isocyanate; and G isan epoxide, isocyanate, benzylic halide, amine, acid halide, ester, oramide.
 3. The process of claim 1 wherein L and L′ are independentlyselected from the group consisting of —Y—R, wherein Y is O, NH, or S andR is alkyl, substituted alkyl, alkaryl, substituted alkaryl, aryl, orsubstituted aryl.
 4. The process of claim 1 wherein L and L′ areindependently selected from the group consisting of optionallysubstituted —NHR″, —OH, and hydrocarbylene-C(═O)OR″; and G is selectedfrom the group consisting of —NH₂, —C(═O)Cl, —C(═O)OR″, or—C(═O)NH—R″—NH₂; wherein R″ is independently hydrogen or an optionallysubstituted hydrocarbyl or hydrocarbylene, and wherein n=2-4, m=0-1, andp=2-3.
 5. The process of claim 1 wherein less than 100% of the reactivependant groups are derivatized to make the derivatized pendant groupsunreactive to the crosslinking agent, wherein the derivatization isperformed either before, during or after contact of the crosslinker withthe polymer substrate.
 6. The process of claim 1 wherein the reactivependant groups are derivatized before the contact of the crosslinkerwith the polymer substrate.
 7. The process of claim 1 wherein thereactive pendant groups are derivatized to contain an optionallysubstituted aliphatic carbon chain with optional —(NZ)-, and —O—linkages, where Z is hydrogen, optionally substituted alkyl oroptionally substituted aryl.
 8. The process of claim 1 wherein thereactive pendant groups are derivatized to contain an optionally linearor branched alkyl group of 1-22 carbon atoms, optionally substitutedwith —O— linkages, and optionally substituted with —NH₂, halogen,hydroxyl, or carbonyl groups, or salts thereof.
 9. The process of claim1 wherein G is —NH₂ and the reactive pendant groups are derivatized witha C₁-C₂₂ alkyl group.
 10. The process of claim 1 wherein up to about 50%of the reactive pendent groups are derivatized.
 11. The process of claim1 wherein up to about 20% of the reactive pendent groups arederivatized.
 12. The process of claim 1 wherein the polymeric backbonecomprises —NZ-, —N⁺ZZ′-, —O—, —C(═O)NZ-, —C(═O)O—, —C(═O)—, —OC(═O)O—,—OC(═O)NZ-, —NHC(═O)NZ-, or —SiZZ′O— linkages, where Z and Z′ areindependently hydrogen, alkyl, substituted alkyl, aryl, or substitutedaryl.
 13. The process of claim 1 wherein the repeat units of thesubstrate polymer comprise aliphatic hydrocarbylene groups withsubstituents comprising one or more of aminoalkyl groups, —C(═O)OZ,—C(═O)X, —C(═O)NZZ′, or —C(═O)NH(CH₂)_(n)NH₂, or salts thereof, where Xis halogen, Z and Z′ are independently hydrogen, C₁-C₂₂ alkyl,substituted alkyl, aryl, or substituted aryl, and n=1-12.
 14. Theprocess of claim 1 wherein substituents on the repeat units are one ormore of —X, —O(Z), —N(ZZ′), —N⁺(ZZ′Z″), —C(═O)OZ, —C(═O)X, —C(═O)NZZ′,—C═N═O, —O—, —N(Z)-, —N⁺(ZZ′)-, —C(═O)N(Z)-, —C(═O)O—, —C(═O)—,—OC(═O)O—, —OC(═O)N(Z)-, —N(Z)C(═O)N(Z′)-, —C(═O)NH(CH₂)_(p)NH₂,—Si(ZZ′)O—, —(OCH₂CH₂)_(m)OH, or —(OSi(ZZ′))_(n)OH, or salts thereof,wherein X is a halogen, Z, Z′, and Z″ are independently hydrogen orC₁-C₂₂ optionally substituted alkyl or aryl, and wherein m is 1 to 50, nis 1 to 100, and p is 1 to
 12. 15. The process of claim 1 wherein therepeat units contain substituents comprising one or more of C₁-C₂₂aminoalkyl groups, optionally substituted with alkyl or aldaroyl groups,or salts thereof.
 16. The process of claim 1 wherein the repeat unit isan azahydrocarbylene or salts thereof with one or more terminal aminogroups or salt thereof as substituents on the N of the azahydrocarbylenerepeat unit.
 17. The process of claim 1 wherein the substrate polymercomprises polyallylamine, polyallylamine hydrochloride, branchedpolyethyleneimine, branched polyethyleneimine hydrochloride,poly(acryloyl chloride), poly(methacryloyl chloride),poly[N-ω-aminoalkyl)acrylamide], polyglycosamine, carboxymethylchitosan,chitosan, chitosan hydrochloride, or derivatives or salts thereof. 18.The process of claim 1 wherein the crosslinking agent is derived from analdaric acid, aldarolactone, aldarodilactone, aldarolactone ester,aldaric acid monoester, aldaric acid diester, or aldaramide, or saltsthereof.
 19. The process of claim 1 wherein the crosslinking agent isderived from glucaric acid, galactaric acid, mannaric acid, xylaric acidor tartaric acid.
 20. The process of claim 1 wherein the crosslinkingagent is selected from compounds having Formulae IX, X, XI, XII:

wherein A1 is independently selected from the group consisting of:

and salts thereof; and A2 is selected from the group consisting of—NH—R₅—NH——NH—R₅—O—and—O—R₅—O— and salts thereof; wherein R₅ and R₇ are independentlyaliphatic or aromatic hydrocarbylene groups, linear or cyclic,optionally substituted with alkyl, aryl, hydroxy, amino, carbonyl,carboxyl, ester, amide, alkoxy, nitrile or halogen, or slats thereof,and optionally containing —O—, —Si(ZZ′)O—, —(C═O)— or —NZ- linkages,where Z and Z′ are independently hydrogen, alkyl, substituted alkyl,alkaryl, substituted alkaryl, aryl, or substituted aryl; and R₆ ishydrogen or a 1-22 carbon alkyl group.
 21. The process of claim 20wherein R₅ and R₇ are independently optionally substituted aliphaticcarbon chains with optional —(NZ)- or —O— linkages, wherein Z ishydrogen, optionally substituted alkyl or optionally substituted aryl.22. The process of claim 20 wherein R₅ and R₇ are independently linear,cyclic, or branched alkylene groups of 1-10 carbon atoms, optionallysubstituted with -0- linkages, and optionally substituted with —NH₂groups, or salts thereof.
 23. The process of claim 20 wherein R₇ is—[(CH₂)₁₋₂₁]—, —CH(CH₃)—, —CH(isopropyl)-, —CH(isobutyl)-,—CH(CH(CH₃)CH₂CH₃)—, —CH(CH₂OH)—, —CH(CH₂CH₂SCH₃)—, —CH(CH(OH)CH₃)—,—CH(CH₂C₆H₅)—, —CH(CH₂C₆H₄OH)—, —CH(CH₂CONH₂)—, or —CH(CH₂CH₂CONH₂)—;and R₅ is —[(CH₂)₂₋₂₂]—, —[(CH₂)₀₋₆(C₆H₁₀)(CH₂)₀₋₆]—,—[CH₂CH₂(OCH₂CH₂)₁₋₂₁]—, —[CH₂CH(CH₃)[OCH₂CH(CH₃)]₁₋₂₁]—,—(CH₂CH₂NH)₁₋₂₂CH₂CH₂—,—[CH₂CH(CH₃)[OCH₂CH(CH₃)]_(x)(OCH₂CH₂)_(y)[OCH₂CH(CH₃)]_(z)]— whereinx+y+z=2-50, —[CH₂CH₂(OCH₂CH₂)_(x)[OCH₂CH(CH₃)]_(y)(OCH₂CH₂)_(z)]—wherein x+y+z=2-50,—[CH(CH₃)CH₂O]_(x)CH₂C(Z′)(CH₂[OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)—wherein x+y+z=2-10 and Z′ is H, methyl or ethyl,—[CH(CH₃)CH₂O]_(x)CH₂CH([OCH₂CH(CH₃)]_(y)—)CH₂[OCH₂CH(CH₃)]_(z)— whereinx+y+z=3-100, or —CH₂CH₂CH₂CH₂[CH(NH₂)CONHCH₂CH₂CH₂CH₂]₀₋₁₀CH(COYR)— orsalts thereof, wherein Y is O or NH, and R is a C₁-C₂₂ optionallysubstituted alkyl, aryl, or alkaryl.
 24. The process of claim 20 whereinabout 0.0005 to about 0.5 molar equivalents of crosslinking agent areused per reactive pendant group.
 25. The process of claim 20 whereinabout from about 0.005 to about 0.5 molar equivalents of crosslinkingagent are used per reactive pendant group.
 26. The process of claim 20wherein 0.01 to 0.25 molar equivalents of the reactive pendant groupsare derivatized.